Effects of DEHP on endometrial receptivity and embryo implantation in pregnant mice.

Di-(2-ethylhexyl)-phthalate (DEHP) is a ubiquitous environmental pollutant and endocrine disruptor (ED) that causes serious adverse effects on animal and human health. The harmful effects of DEHP on human reproduction are increasingly recognized, especially in women. However, it is not known how endometrial receptivity and embryo implantation, which play important roles in the establishment of pregnancy, are affected by DEHP. This study was aimed towards investigating the effects of DEHP on endometrial receptivity and embryo implantation in pregnant mice. The pregnant mice received DEHP at 0, 250, 500 and 1000 mg/kg/day from day 1 (D1) of gestation until sacrifice. Administration of DEHP led to compromised endometrial receptivity and decreased number of implantation sites. The mRNA and protein expression levels of ERα, PR and E-cadherin, but not those of HoxA10 and MMP-2, were up-regulated by DEHP in the mouse endometrium. The results further suggested that DEHP disrupts the MAPK and NF-κB signaling pathways. This was maybe one of paths which influenced the E-cadherin expression. In conclusion, DEHP reduced endometrial receptivity and impaired embryo implantation by influencing the expression of hormone receptors and E-cadherin. Therefore, determining the full extent of the hazards of DEHP to human reproduction will be vital to developing and implementing effective protective measures.